Polynitro halo compounds useful as antibiotics,fungicides and explosives

ABSTRACT

A NEW COMPOSITION OF MATTER, METHYL 2,2-DINTROPROPYL CARBONATE, IS DISCLOSED HAVING FUNGICIDAL ACTIVITY.

United States Patent US. Cl. 260-463 Claim ABSTRACT OF THE DISCLOSURE Anew composition of "matter, methyl 2,2-dinitropropyl carbonate, isdisclosed, having fungicidal activity.

This is a division of application Ser. No. 326,286, filed Nov. 26, 1963,now Pat. No. 3,359,334.

This invention relates to certain novel halo dinitro compounds and theirmethod of preparation.

It is an object of this invention to prepare certain novel organiccompounds. It is another object of this invention to prepare new nitrocompounds in a novel manner. Still another object of this invention isto provide novel antibiotic and antifungal compositions. These and otherobjects of this invention will be apparent from the detailed descriptionwhich follows.

One type of the novel compounds of this invention has the followinggeneral formula:

wherein A is lower alkylene, preferably of from 1 to 6 carbon atoms andR is a lower alkyl radical of from 1 to 6 carbon atoms;

-A -CN wherein A is an alkylene radical preferably having from 1 toabout 20 carbon atoms;

ollh

A4(HJNR'4 wherein A is an alkylene radical, preferably from 1 to about20 carbons; and R and R, are the same or difierent and are selected fromthe group consisting of hydrogen, hydrocarbyl, preferably alkyl or arylhaving from 1 to about 12 carbons, w-hydroxyalkyl preferably having from1 to about 12 carbons;

-A5('.I7O-A5- wherein A are alkylene, preferably of from 1 to carbons;

wherein A and R are alkylene, preferably of from 1 to 20 carbons;

wherein the A groups are alkylene, preferably of from 1 to 20 carbons;and R is alkylene, preferably of from 1 to 20 carbons or vinylene(CH--CH); n is an integer of from 1 to 2 and being equal to the valenceof R; and X is chloro or bromo.

Illustrative compounds within the scope of Formula I include:

S-chloro-S,S-dinitro-Z-hydroxy pentane, 6-bromo-6,6-dinitro-3-hydroxyhexane, 5-bromo-5,5-dinitro-1,2-pentanediol,l-chloro-l,1-dinitro-2-cyanoethane, l-bromo-1,1-dinitrovaleronitrile,N-butyl-3-chloro-3,3-dinitropropionamide,N-decyl-S-chloro-S,S-dinitropentanamide,N-w-hydroxyethyl-4-dinitrobutyramide,N,N-diethyl-4-chloro-4,4-dinitrobutyramide,2-chloro-2,Z-dinitroethyl-6-chloro-6,6-dinitrohexanoate,4-chloro-4,4-dinitrobutyl-4-chloro-4,4-dinitrobutyrate, 1,3 -bis-(4-chloro-4,4-dinitrobutyryloxy) -pr0pane, 1,IO-bis(4-chloro-4,4-dinitrobutyryloxy)-decane, 1, 8-bis- (3-chloro-3,3-dinitropropionyloxy) -octane,bis-(3-chloro-3,3-dinitropropyl) adipate,bis-'(3-chloro-3,3-dinitropropyl) maleate,bis-(S-chloro-S,S-dinitropentyl) adipate,bis-(S-chloro-S,S-dinitropentyl) maleate'bis-(5-bromo-5,5-dinitropentyl) octanedioate,bis-(S-bromo-S,S-dinitropentyl) maleate, bis-(2-chloro-2,2-dinitroethyl)dodecanedioate, bis-(2-chloro-2,2-dinitroethyl) maleate,

In general, the compounds of Formula I are prepared by reacting chlorineor bromine with the corresponding salt of an organic gem-dinitrocompounds in accordance with the following general reaction:

wherein A, R, X and n are as defined above, and M is an alkali oralkaline earth metal such as sodium, potassium, lithium, or calcium.

Alternatively, certain of the compounds of Formula I may be prepared byprocedures other than that set forth in Equation II. These alternativereactions are hereinafter set forth.

When R in Formula I is the halo dinitro compounds of this invention areprepared according to the following reaction equation:

wherein X, A R and R, are as defined above and Z is chloro, bromo orhydroxy. where R is 3 in Formula I, the preparation is in accordancewith the following general reaction:

wherein X and A are as defined above and Z is lower alkyl, i.e., from 1to 6 carbons.

Where R is -A.i 3oR6o i-Au in the above Formula I, the reaction is asfollows:

wherein X, R and A are as defined above and Z is hydroxy, chloro orbromo.

When R is II II A7OCR7COA7 in Formula I, the reaction scheme is inaccord with the following N02 I X( J-A1O( 1R1i) wherein X, A; and R areas defined above and Z is hydroxy, chloro or :bromo.

The above reaction is conveniently carried out in any inert polar ornonpolar solvent in which the reactants are soluble, i.e., water,methanol, ethanol, benzene, chloroform, etc. The proportions of thereactants employed in the reaction are not critical. Normally,stoichiometrically equivalent amounts are used since this results in themost economical utilization of the reactants. The reaction temperatureshould normally be sufliciently high so that the reactants will dissolveto a substantial degree in the reaction medium, but in any event, thereaction temperature should be below the composition temperature of thereactant. Normally, the reaction is conducted at a temperature betweenabout C. and about +120 C. The most preferred temperature is from aboutl0 C. to about 50 C. Pressure is not critical in this reaction.Therefore, while any pressure can be used, the reaction is normally rununder atmospheric pressure. Agitation of the reactants such as bymechanical stirrer, while desirable in that it increases the reactionrate, is not necessary. The novel compounds of this invention may beisolated in conventional manner such as by extraction, distillation and/or filtration.

In the esterification reaction indicated above in Equations III to VI,it may be desirable in some cases in order to increase the reactionrate, to include in the reaction mixture a small, effective catalyticamount (0.1% to about 20% by weight based on total weight of reactants)of an acid esterification catalyst such as aluminum trichloride orpolyphosphoric acid.

To more clearly illustrate our invention the following examples arepresented. It is to be understood, however, that these examples areintended merely as an illustrative embodiment of the invention. In theexamples, the percentages are by weight unless otherwise indicated.

EXAMPLE I Preparation of bis-(2-chloro-2,2-dinitroethyl) maleate To asolution of 83 g. 2,2-dinitropropane-1,3-diol in 150 ml. methanol at 0C. was added, in portions, With shaking and hand-stirring, a coldsolution of 32.5 g. potassium hydroxide in 150 ml. methanol. The lightyellow potassium 2,2-dinitroethanol precipitated immediately. Afterstanding in ice for half an hour, it was filtered and Washed well withcold methanol. The wet filter-cake was suspended in 250 ml. water, and,with good stirring, chlorine introduced at 0 C. to 5 C. After 40minutes, all the salt had disappeared and an oil had separated on thebottom of the fiask. The mixture was light green; it was stirred for 15minutes longer, the oil separated and the aqueous phase extracted threetimes with diethyl ether. The oil and other solution were combined anddried over sodium sulfate. Removal of the solvent under vacuum left avery light green, slightly lachrymatory oil. Distillation at 0.4 to 0.5mm. and 57.5 to 60 C. yielded 41 g. (0.24 mole) of 2-chloro-2,2-dinitroethanol. The 2-chloro-2,Z-dinitroethanol is thenreacted with 0.14 mole of maleic acid at 50 to 60 C. Thebis-(2-chloro2,2-dinitroethyl) maleate is obtained in good yields.

EXAMPLE II Preparation of methyl 4-chloro-4,4-dinitrobutyrate A 500 ml.round-bottom 3-neck flask was fitted with mechanical stirrer,thermometer, and dropping funnel. It was charged with 57.2 g. (0.258mole) crude methyl 5-hydroxy-4,4-dinitropentanoate [Klager, Journal ofOrganic Chemistry 16, 162463, (1951)] in 150 ml. methanol. At 015 C.solution of 6.8 g. sodium (0.30 mole) in ml. methanol was added dropwiseover 30 minutes. Stirring was continued for an additional 45 minutes.The yellow sodium salt of methyl 4,4-dinitrobutyrate salt was collectedon a filter and washed with cold methanol. The wet salt was dissolved in200 ml. water to a total volume of 250 ml. Then 82 ml. of the aqueoussolution was charged to a 300 m1. round-bottom 3-neck flask fitted withstirrer, thermometer and gas inlet tube. At 5 C., chlorine wasintroduced with stirring. The temperature rose to 14 C. in 5 minutes,and a heavy yellow oil separated. Stirring was continued for 5 minutesafter the temperature began to fall, while a slow stream of chlorine wasintroduced. The oil was separated, and the aqueous phase Was extractedonce with ml., then with 40 ml. diethyl ether. The combined extractswere washed with 200 ml. Water, and dried over sodium sulfate. Followingremoval of solvent by evaporation, the residue was submitted to vacuumdistillation. Two fractions were collected.

(1) B.P. 60 to 66 at 0.15 mm., 1.0 g., 11 1.4614 (11) B.P. 66 to 69 at0.15 mm., 7.1 g., H1324 1.4615

Both were colorless liquids, and were combined.

Elemental analysis.--Calcd for C H N O Cl (percent) C, 26.58; H, 3.12;Cl. 15.64. Found (percent): C, 26.52; H, 3.38; Cl. 16.75.

EXAMPLE 3 2-bromo-2,2-dinitroethy1 4-bromo-4,4-dinitrobutyrate To 5.0 g.of 4% oleum (prepared by adding g. of 30% fuming sulfuric acid to 100 g.of 96% sulfuric acid) was added 1.08 g. (0.0050 M)2-bromo-2,2-dinitroethanol and 1.36 g. (0.0050 M) methyl4-bromo-4,4-dinitrobutyrate. Both substances dissolved readily with aslight rise in temperature. The solution was very light yellow. Afterthree days at room temperature, a few drops of the reaction mixture wasstirred with ice; no solid was obtained. The reaction mixture was keptin an oil-bath at 50 C. for 22 hours. No solid product was isolated withice. The temperature of the oil-bath was raised to 75 C., and maintainedthere for 20 hours. The reaction mixture was poured on ice withstirring; a nearly colorless, waxy solid separated. After thoroughlywashing with water, the solid was left to dry on a porous plate. Thecrude ester weight 0.50 g. (22%), M.P. 66 to 72 C. Recrystallizationfrom diisopropyl ether gave colorless product, M.P. 71.5 to 73 C.

Elemental analysis.Calcd (percent): C, 15.87; H, 1.33; N, 12.34. Found(percent): C, 16.03; H, 1.32; N, 12.68.

When the above example was repeated using 2-chloro- 2,2-dinitroethanoland methyl 4-chloro-4,4-dinitrobutyrate (prepared according to ExampleII) in lieu of 2-bromorate, respectively, 2-chloro-2,2-dinitroethyl4-chloro-4,4- dinitrobutyrate is obtained in good yields.

EXAMPLE IV 4-bromo-4,4-dinitrobutyranilide Fifteen grams (0.058 M)4-bromo-4,4-dinitrobutyric acid and thirty milliliters (0.42 M) thionylchloride were refluxed for 45 minutes. The excess thionyl choride wasremoved under vacuum, and the acid chloride recovered by distillation. Asolution of 5.83 g. (0.0212 M) of the 4-bromo-4,4-dinitrobutyrylchloride in 10 ml. benzene was added gradually, over 45 minutes, to asolution of 3.72 g. (0.04 M) aniline in 7 ml. benzene at reflux. Theprecipitate which formed when the aniline solution was added tended todissolve at the beginning, but complete solution was not attained. Themixture darkened as the reaction proceeded. The walls of the flask wererinsed with to ml. fresh benzene, and refluxing continued for thirtyminutes. After cooling, an attempt to extract the aniline hydrochloridewith water caused crystallization of the crude product in the separatoryfunnel. The anilide was dissolved with heating. The benzene solution,while still warm, was washed twice with water, boiled to remove waterazeotropically, and, after cooling, treated with an equal volume ofhexane. The crude product was filtered, washed with hexane, andair-dried. Wt. 4.8 g. (68%) M.P. 116 to 121. On standing, an additional0.3 g. (M.P. 90 to 126) was collected from the mother liquor and wash.The crude, tan anilide (4.8 g.) was recrystallized from 70 ml.isopropanol and ml. water, and de colorized twice with charcoal. Theproduct was very light yellow; wt. 2.9 g. (corresponding to a 43% yield)M.P. 133 to 135. A small sample, recrystallized again from aqueousisopropanol, was still light yellow and melted at 134 to 136.

Elemental analysis.Calcd (percent): 0,3616%; H, 3.04; N, 12.65; Br,24.05. Found (percent): C, 36.75; H, 3.23; N, 12.46; Br, 24.34.

When the above example is repeated employing ethylamine in lieu ofaniline and 4-chloro-4,4-dinitrobutyric acid in place of4-bromo-4,4-dinitrobutyric acid, N-ethyl- 4c'hloro-4,4-dinitrobutyramideis obtained.

EXAMPLE V 1,4-bis- (4-bromo-4,4-dinitrobutyryloxy)-butane4-bromo-4,4-dinitrobutyryl chloride (5.22 g., 0.0203 M) was added to1,4-butanediol (0.79 g., 0.0088 M). The reaction mixture became hot, andhydrogen chloride was evolved. The clear viscous light yellow mixturewas placed in an oil-bath at 85 to 100 for minutes; it was taken up inabout 10 ml. benzene, and the product precipitated by the gradualaddition of 30 ml. hexane. The colorless 6 crystals were collected andwashed with hexane; wt. 4.0 g. (76%), M.P. 80 to 82. A small samplerecrystallized twice (for elemental analysis) from benzene-hexane meltedat 84 to 86. The main portion (3.6) was recrystallized once frombenzene-hexane (1:1); wt. 3.1 g. (86% recovery), M.P. 84 to 86.

Elemental analysis.Calcd (percent): C, 25.37; H, 2.84; N, 9.86; Br,28.14. Found (percent): C, 26.15; N, 3.00; N, 9.59; Br, 28.38.

When the above example is repeated using 4-chloro-4,4- dinitrobutyrylchloride in place of 4-bromo-4,4-dinitrobutyryl chloride and ethyleneglycol in lieu of 1,4- butanediol, a good yield ofbis-(4-chloro-4,4-dinitrobutyryloxy) ethane is obtained.

EXAMPLE VI Bis-(2-bromo-2,2-dinitroethyl) adipate 2-bromo2,2-dinitroethanol (5.5 g., 0.0255 M), adipyl chloride (2,2 g., 0.012M), and 2 drops of concentrated sulfuric acid were heated on the steambath. Evolution of hydrogen chloride began almost immediately. After 45minutes, the reaction mixture was poured into ice and water. Theprecipitated ester was broken up in a mortar and washed with water. Theester was then slurried on the funnel with one normal sodium carbonatesolution, filtered, and washed well with Water. Five and one half gramsof crude product (M.P. 70 to 74) were obtained after air drying. Theester was purified by dissolving in 25 ml. benzene, charcoaling, andadding 35 ml. hexane to the hot filtrate. Crystallization took place at20. The adipate was filtered, washed with cold hexane, and dried; weight4.5 g. (70%), M.P. 72 to 74. A small sample was again recrystallizedfrom benzene-hexane for elemental anaylsis (M.P. 74 to 76).

Calcd (percent): Br. 29.57. Found (percent): 28.78.

EXAMPLE VII Bis- (2-chloro-2,2-dinitroethyl) adipate2-chloro-2,2-dinitroethanol (11 g. 0.065 M), adipyl chloride (5.5 g.,0.030 M), and 4 drops of concentrated sulfuric acid were heated on thesteam-bath for 30 minutes. Evolution of hydrogen chloride began even onmixing in the cold. The light-yellow solution was poured into ice andwater. The light tan semi-solid which resulted after a few minutesstirring could not be broken up into small particles in a mortar. It waswashed successively with water, one normal sodium carbonate solution,and again with water, as well as possible and left to dry on a porousplate. The crude ester (10 g., M.P. 32 to 40) was recrystallized from 35ml. diisopropyl ether. The mixture was chilled at --20 and the crystalscollected, washed with cold solvent, and dried; weight 6.0 g. M.P. 38 to48. A small sample was again recrystallized from diisopropyl ether (M.P.49 to 51) and submitted for elemental analysis:

Calcd (percent): CI, 15.73. Found (percent): CI, 16.09.

The main portion of the ester was recrystallized a second time fromdiisopropyl ether (20 ml.), and 3.8 g. (28%) of product, M.P. 47 to 52,collected.

When the above example was repeated using sebacic acid in lieu of adipylchloride, bis-(2-chloro-2,2-dinitroethyl) sebacicate was obtained.

EXAMPLE VIII Preparation of l-chloro-1,1-dinitrobutyronitrile To onemole of 1,1-dinitrobutyronitrile (prepared by the addition of one moleof dinitromethane to one mole of acrylonitrile) is added 1 M potassiumhydroxide at about 40 to 50 C. to form the potassium salt of1,1-dinitrobutyronitrile. About grams of the salt is then dissolved inabout 2 liters of water. Then 100 ml. of this aqueous solution ischarged to a 300 ml. round-bottom 3- neck flask fitted with stirrer,thermometer and gas inlet tube. At to 10 C., chlorine gas is introducedwith stirring. The addition of chlorine is continued for about 0.5 hour.The water is removed by evaporation under vacuum. The productl-chloro-l,l-dinitro-3-cyano propane is obtained in good yields.

When the foregoing example is repeated utilizing 1,1-dinitro-3-methyl-butyronitrile in lieu of 1,1-butyronitrile,l-chloro-1,1dinitro-3-methyl-butyronitrile is obtained.

EXAMPLE IX Preparation of -chloro-5,5-dinitr0-1,2-pentanediol To onemole of 5,5-dinitro-l,2-pentanediol (prepared by the addition of onemole of hydrogen peroxide to one mole of 5,5,5-trinitro-1,2-pentanediol)is added 1 M potassium hydroxide at about 40 to 50 C. to form thepotassium salt of 5,5-dinitro-1,Z-pentanediol. About 100 grams of thesalt is then dissolved in about 2 liters of water. Then 100 ml. of thisaqueous solution is charged to a 300 ml. round-bottom 3-neck flaskfitted with stirrer, thermometer and gas inlet tube. At 0 to C.,chlorine gas is introduced with stirring. The addition of chlorine iscontinued for about 0.5 hour. The water is removed by evaporation undervacuum. The product 5-chloro-5,5-dinitro-1,2-pentanediol is obtained ingood yield.

When the foregoing example is repeated utilizing 5,5- dinitro-2-pentanolin lieu of 5,5-dinitro-1,2-pentanediol, 5-chloro-5,5-dinitro-2-pentanolis obtained. 1

In addition to the novel compounds within the scope of Formula I arestill another class of novel polynitro compounds. The compounds have thefollowing general formula:

VI! N02 0 wherein A is a lower alkylene group preferably having from 1to about 6 carbon atoms such as methylene, ethylene, butylene andhexarnethylene; R is a lower alkyl group preferably having from 1 toabout 6 carbon atoms such as methyl, ethyl, butyl and hexyl; and Y ishydrogen or alkoxy, preferably lower alkoxy of from 1 to 8 carbons suchas ethoxy (--OC H methoxy (-OCH etc.

Typical of the compounds within the scope of Formula VII are:2,2-dinitrobutyl formate, 3,3-dinitrooctyl formate, 5,5-dinitrohexylformate, ethyl-2,2-dinitropropyl carbonate, hexyl-4,4-dinitrodecylcarbonate, isopropyl-2,2 dinitropropyl carbonate and propyl2,2-dinitropropyl carbonate.

The novel esters of the above formula are prepared in accordance withthe following general reaction.

(VIII) NO 2 N0 wherein A R and Y are as defined above; and Z is hydroxyor halogen, preferably chlorine or bromine.

The above reaction is conveniently, although not necessarily carried outin any inert solvent in which the reactants are soluble, i.e., benzene,toluene or hexane. The proportions of the reactants employed in thereaction are not critical. Normally, stoichiometrically equivalentamounts are used since this results in the most economical utilizationof the reactants. Thus, usually one mole of alcohol is used per mole ofacid or halo carbonate. The reaction temperature should normally besufficiently high so that the reactants will dissolve to a substantialdegree in the reaction medium, but in any event, the reactiontemperature should be below the composition temperature of the reactant.Normally, the reaction is conducted at a temperature between about 0 C.and about 100 C. The most preferred temperature is from about C. toabout 75 C. Pressure is not critical in this reaction. Therefore, whileany pressure can be used, the reaction is normally run under atmosphericpressure.

The above reaction is preferably conducted in the presence of aneffective catalytic amount of an acid esterification catalyst such asaluminum chloride or boron trifluoride.

EXAMPLE X 2,2-dinitropropyl formate To a solution of 16.0 g. (0.10 M,pure) 2,2-dinitropropanol in 22 ml. formic acid (98 to was added aspatula-tip of anhydrous aluminum chloride. After refluxing for 23hours, the mixture was poured into ice-water and the crude esterseparated with the aid of 30 ml. methylene chloride. The organic phasewas extracted first with 50 ml., and then with 25 ml. of cold one normalsodium hydroxide solution, washed twice with water, and dried overnight.Removal of the solvent in vacuo left 2.0 g. (11% of theory) of verylight green liquid, n 1.4486. Distillation at 72.5 to 73.5 C./0.6 mm.gave a colorless distillate, 11 1.5587.

Elemental analysis.Calcd for C H N O (percent): C, 26.97; H, 3.40; N,15.73. Found (percent): C, 27.33; H, 3.37; N, 15.60.

When the foregoing example is repeated substituting 3,3-dinitrobutanolfor 2,2-dinitropropanol, a good yield of 3,3-dinitrobutyl formate isobtained.

EXAMPLE XI Methyl 2,2-dinitropropyl carbonate B.P., degrees mm Grams71.13 Grams Percent I $73 0. 6 1. 4 1 4485 II 73-76 0.4-0. 5 7.8 1 44869 0 54 III 76 0. 4-0 5 1. 2 1 4487 The residue (0.7 g.) was slightlyviscous and light brown in color. The crude carbonate (Fractions I, IIand III combined) was dissolved in 25 ml. methylene chloride. It wasextracted twice with cold solutions of 20 and 10 ml., respectively, ofone normal sodium hydroxide, washed twice with water, and dried oversodium sulfate. The carbonate after removal of the solvent weight 4.8 g.n 1.4422. On vacuum distillation, the following fractions werecollected:

(I) 88 to 93 0.6 mm. 1.6 g. 11 14422 (II) 93 to 94 0.6 mm. 2.4 g. 111.4425 (III) 94 0.6 mm. 0.1 g.

Fraction II showed no presence of hydroxyl in the infrared spectrum.

Elemental analysis (II).Calcd for C H N O (percent): C, 28.85; H, 3.87;N, 13.46. Found (percent): C, 29.49; H, 4.37; N, 13.92.

When the above example is repeated using 3,3-dinitro-1- pentanol in lieuof 2,2-dinitropropanol, and ethyl bromoformate in place of methylchloroformate, a substantial quantity of essentially pureethyl-3,3-dinitropropyl carbonate is obtained.

The compounds of this invention, which contain a plurality of nitrogroups, are inherently useful as high explosives. These compounds canalso be used in any con ventional explosive missile, projectile, rocketor the like, as the main explosive charge. An example of such a missileis described in U.S. Pat. 2,470,162, issued May 17, 1949. One way ofusing such high explosives in a device such as that disclosed in U.S.Pat. 2,470,162 is to absorb the liquid explosive in an absorbentmaterial such as cellulose, wood pulp, or sawdust. The resultantdynamite-type explosive can then be packed into the warhead of themissile. A charge thus prepared is sufliciently insensitively towithstand the shock entailed in the ejection of a shell from a gunbarrel or a rocket launching tube under the pressure developed fromignition of a propellant charge, and can be caused to explode onoperation of an impact or time-fuse mechanism firing a detonatingexplosive such as lead azide or mercury fulminate.

Certain of the novel compounds of this invention are also useful asfungicides, in the prevention of bacterial growth, and as plasticizersfor solid rocket propellant formulations.

This example describes a particular method of preparing a novelpropellant composition from the following ingredients employing methyl2,2-dinitropropyl carbonate as a plasticizer:

EXAMPLE XII Ingredient: Wt. percent Ammonium perchlorate 66.00 Aluminum16.00 Copper chromite 0.50 Phenyl betanaphthylamine 0.20 Ferricacetylacetonate 0.08 Glycerol monoricinoleate 1.00 Polypropylene glycol(M.W.=2000) 10.84 Dioctyl azelate 3.00 Methyl 2,2-dinitropropylcarbonate 0.20 Lecithin 0.20 Tolylene diisocyanate 1.98

The aluminum powder is stirred into about /a. of the required volume ofpolypropylene glycol and glycerol monoricinoleate. The mixture isprepared in a stainless steel container, using a copper-berylliumspatula. Mixing is continued for about ten minutes.

The aluminum slurry is added to a conventional mixer equipped withfacilities for heating, cooling and vacuumizing the propellant mix. Thewalls of the aluminum slurry container are scraped thoroughly. Thecontainer is rinsed with /2 of the required volume of dioctyl azelateand the rinses are added to the mixer. The remaining polypropyleneglycol is added to the mixer. The methyl 2,2-dinitropropyl carbonate ismixed with the remaining dioctyl azelate until homogeneous and thesolution is then added to the mixer.

With the mixer off, the ferric acetylacetonate, phenylbetanaphthylarnine, and lecithin are added through a 40- mesh screen.The copper chromite is added to the mixer.

The mixer is covered and mixed by remote control for minutes under 26 to28 inches of vacuum, after which it is stopped and the vacuum releasedwith dry nitrogen. The cover is removed from the mixer and the oxidizeris added by remote control with the mixer blades in motion.

After all of the oxidizer has been added, the mixer is stopped andscraped down. The propellant mass is mixed for 15 minutes at 70 F. under26 inches vacuum by remote control. The mixer is stopped and the vacuumreleased with dry nitrogen. The tolylene diisocyanate is added, afterwhich the mass is mixed for ten minutes at 70 F. and 26 inches of vacuumby remote control. The vacuum is then released with dry nitrogen and themixture is cast.

Propellants prepared in the foregoing manner have a specific impulse inthe range from 225 to about 250 seconds.

The compounds of Formula I are especially useful as antibiotics and asanti-fungals. In this respect, the compounds of Formula I wherein X ischloro are far superior in effectiveness to the corresponding bromocompounds.

with the procedures of this invention are the ether compounds having thegeneral formula:

wherein A is a lower alkylene group preferably having from 1 to about 6carbons, R is a lower alkyl radical preferably having from 1 to about 6carbons and X is hydrogen or nitro. Typical compounds within the scopeof Formula X include 2-nitropropyl 2,2,3,3-tetrafluoro propyl ether and2,2-dinitropropyl 2,2,3,3-tetrafluoro proply ether. The compounds ofFormula X and their method of preparation are disclosed in greaterdetail in Assignees copending U.S. application Ser. No. 326,284 filedNov. 26, 1963, now Pat. No. 3,399,240.

Other classes of compounds which can be used as antifungals according toour invention are:

wherein both A groups are lower alkylene froml to about 6 carbons, andthe R groups are alkyl of from 2 to 6 carbons;

wherein both R groups are lower alkyl, preferably of from 1 to 6carbons; and

wherein R in each instance is lower alkyl of from 1 to about 6 carbons.

The compounds of Formula XI, and their method of preparation aredisclosed in assignees copending U.S. patent application Ser. No.326,287, filed Nov. 26, 1963, now abandoned.

The compounds of Formula XII, and their method of preparation aredisclosed in assignees copending U.S. patent application Ser. No.326,285, filed Nov. 26, 1963, now Patent No. 3,492,311.

The compounds of Formulae XIII and XIV, and their method of preparationare disclosed in assignees copending U.S. patent application Ser. No.326,288, filed Nov. 26, 1963, now Pat. No. 3,306,929.

In the anti-bacterial test a compound within the scope of Formula I wascompared in vitro to pencillin against B. subtillis (gram positivebacteria) and to chloromycetin against E. coli (gram negative bacteria).The compound tested was the compound of Example II, methyl4-chloro-4,4-dinitrobutyrate.

EXAMPLE XIII Two glass plates were uniformly and completely coated witha sterile aqueous solution of gum agar pH 5.7. The agar film wasinoculated with the B. subtillis. Upon each plate was then placed asmall 0.10 ml. glass cylinder, one filled with a standard solution ofpenicillin containing 0.001 mg. per milliliter, on the other plate anaqueous solution of the methyl-4-chloro-4,4-dinitrobutyrate containingone mg. per milliliter. The plates were then incubated by maintainingthem at a temperature of about 37 C. After about 1'5 hours a clear zoneof growth inhibition around each of the cylinders could be observed. Thearea of the zone of growth inhibition around the cylinder containingmethyl-4-chloro-4,4-dinitrobutyrate was somewhat greater than the areaof the zone of growth inhibition around the cylinder containing thestandard penicillin solution.

EXAMPLE XIV Two glass plates were uniformly and completely coated with asterile aqueous solution of gum agar. The agar film was inoculated withthe E. 0011'. Upon each plate was then placed a small glass cylinder,one filled with a standard solution of penicillin containing one unitper milliliter, on the other plate an aqueous solution of themethyl-4-chloro-4,4-dinitrobutyrate. The plates were then incubated at atemperature of about 37 C. After about 15 hours a clear zone of growthinhibition around each of the cylinders could be observed. The area ofthe zone of growth inhibition around the cylinder containingmethyl-4-chloro-4,4 dinitrobutyrate was somewhat greater than the areaof the zone of growth inhibition around the cylinder containing thestandard penicillin solution.

Anti-fungal tests were conducted using compounds within the scope ofFormulae IX to XIV. In each of these tests the test organism wastrichophyton mentagrophytes.

EXAMPLE XV The drug was placed on the surface of an inoculated agarplate prepared in accordance with Example XIV, and the zone ofinhibition caused by the test compound (0.1 mg./ml.) compared with thatproduced by a solution of undecylenic acid, (0.1 mg./ml.) a standardcommercial fungicide. The results of the testing was evaluated inaccordance with the following scale.

SCALE Inactive 1-Poor, (less active than undecylenic acid) 2G0od,approximately equal to undecylenic acid) 3-Excellent, (at least 2.5times more active than undecylenic acid) The results obtained inaccordance with the above-described anti-fungal tests are set forth inthe following table.

TABLE 1 Compound: Rating Methyl 4-chloro-4,4-dinitrobutyrate (Compoundof Formula I) 3 2,2 dinitropropyl formate (Compound of Formula VII) 3Bis (2,2 dinitrobutyl) maleate (Compound of Formula XI) 3 12 Methyl2,2-dinitropropyl carbonate (Compound of Formula VII) 3 Cyclic sulfiteof 2,2-dinitro-1,3-propanediol (Compound of Formula XII) 3 Cyclic phenylphosphite of 2,2 dinitro-l,3-propanediol (compound of Formula XII) 32,2-dinitropropyl-2,2,3,3 tetrafluoro propyl ether (compound of FormulaIX) 3 5,5,5-trinitro 1,2 pentanediol diacetate (compound of Formula XIV)3 2,2-dimethyl 4(3,3,3' trinitropropyl) 1,3-dioxolane (compound ofFormula XIII) 3 Bis-(2, dinitropropyl maleate 2 Bis-(2-bromo-2,2dinitroethyl) adipate 2 Application of the antibacterial and antifungalcompounds of this invention for the various purposes disclosed may bemade from solutions in suitable solvent carriers, such as alcohol,benzene, and petroleum naphtha, or from dispersions in aqueous or othermedia, or in the form of a dust. They may be used in combination withsupplementary agents, such as talc, bentanite, tricalcium phosphate,various clays, spreading agents, stickers and other adjuvants commonlyused in bacteria and fungus control compositions. They may also be usedin combination with other bacteria and fungus control agents, such assulfur fungicides or organic fungicides and various other agentscommonly used in fungicidal and insecticidal applications. When thebactericides and fungicides of this invention are used in conjunctionwith adjuvants, the active ingredient is employed in a bactericidally orfungicidally effective amount, normally from about 0.01% to by weight ofthe total composition. Caution should be used in using these productssince many of them are irridant to the skin.

It will be understood that various modifications may be made in thisinvention without departing from the spirit thereof or the scope of theappended claim.

We claim:

1. As a composition of matter, 2,2-dinitropropyl methyl carbonate,having the structural formula:

MeC (N0 CH OCOOMe References Cited UNITED STATES PATENTS 3,396,1878/1968 Benziger et al. 260463 2,379,252 6/1945 Muskat et a1 260--4632,377,111 5/1945 Strain et al. 260-463 2,231,936 2/1941 Medick 2604633,120,554 2/1964 Kirkwood et al. 260-463 2,801,256 7/1957 Sonntag260410.9 2,155,625 12/1935 Von Retze 260-488 OTHER REFERENCES Kissingeret al., J. Organic Chem., 26, 5203-5205 (1961).

Groggins, Unit Processes in Organic Synthesis, 3rd ed. (1947) p. 640.

BERNARD HELFIN, Primary Examiner L. D. CRESCENTE, Assistant Examiner US.Cl. X.R.

260-327H, 340.9, 478, 485]. 485Gr, 488F, 614F, 961, 424222, 278, 301,303, 311, 313, 314

